Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

Some reasons for the lack of progress in the treatment of acute myelogenous leukemia: a review of three consecutive trials of the treatment of poor prognosis patients

The failure of three consecutive treatment protocols to significantly increase the complete remission rate for poor prognosis newly diagnosed patients with acute myelocytic leukemia led to a detailed investigation of the causes of treatment failure. In the majority of cases treatment failure was attributable to "clinical resistance" to therapy. Upon close examination two types of "clinical resistance" were discernible: the failure of chemotherapy to produce adequate cytotoxic effects ("classical" drug resistance), and treatment failure attributed to the rapid regrowth of leukemia cells subsequent to the substantial killing of leukemia cells by cytotoxic therapy ("biological" resistance). Each form of resistance accounted for one-half of the treatment failures.     

Clinical and economic evaluation of benzodiazepines: a value analysis

Benzodiazepines are one of the most frequently prescribed classes of medications in the world. Thought to relieve the symptoms of anxiety, insomnia, epilepsy, and some less common conditions, these medications are supported by a body of clinical trials demonstrating efficacy. However, there is also literature that suggests problems of abuse and dependence, along with some serious adverse effects. The present article utilises a value-analysis strategy to outline the clinical efficacy and economic efficiency of benzodiazepines from a variety of perspectives including those of the patient, physician and manufacturer. Results of this analysis suggest that these medications are effective when used appropriately, but that implementation of appropriate use is difficult. Remedies to this situation are discussed.     

Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses

Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens.     

24-hour unit dose dispensing of class III-V controlled substances

Methods of controlling controlled substance (CS) inventories in unit dose dispensing systems vary. The two extremes are total floor stock of all CS drugs by the use of declining inventory signout sheets on the nursing unit to controlling only Class II and a few selected class III-V items. The method described herein outlines a systematic approach to controlling items on an individual patient basis consistant with the benefits of unit dose dispensing. A CS card assigned to each patient for each of his required controlled substance medications serves as an audit trail for doses consumed by the patient and provides a declining inventory receipt when returned to the pharmacy.     

Clinical studies of a fast homoarginine-sensitive alkaline phosphatase in patients with cancer

The activity of an isoenzyme of alkaline phosphatase (FHAP) was measured in serum samples obtained from 1692 individual subjects. The median FHAP concentration in patients with untreated or recurrent cancer (2.73 IU/liter) was two-fold higher than in hospitalized control patients with illnesses other than cancer (1.17 IU/liter) and three-fold higher than in healthy control subjects (0.93 IU/liter). Among patients with either breast or colorectal cancer who were clinically disease free following their initial therapy, the median FHAP concentration (1.54 IU/liter) was intermediate between the median FHAP concentration in patients with untreated or recurrent cancer and that of healthy control subjects. In order to illustrate the potential clinical application of FHAP as a diagnostic cancer marker, we have selected a serum FHAP concentration of 2.22 IU/liter as a reference value above which only 3% of healthy control subjects would have a "positive" test. Utilizing this reference value, 58% of the patients in the present study with untreated or recurrent cancer would have a positive FHAP test, whereas only 11%, of hospitalized patients with illnesses other than cancer would have a positive test. These data suggest that FHAP may be equivalent to the carcinoembryonic antigen as a diagnostic cancer marker.     

Professionalism: rise and fall.

Historically, the early professionalization movements in medicine and the law appear as organizational projects which aspire to monopolize income and opportunities in markets of services or labor and to monopolize status and work privileges in occupational hierarchies. Their central task is to standardize training and link it to actual or potential markets of labor or services, a linkage that is structurally effected in the modern university. The second wave of professionalization has different protagonists than the older "market professions": placed in a different structural situation, the bureaucratic professions transform the model of profession (which they adopt as a strategy of collective ascension) into an ideology. The import of the ideology of professionalism is examined in relation to two issues: the relationships between professional occupations and bureaucratic organizations; and the position of professional occupations within the larger structure of inequality. Analysis of the first point requires consideration of the distinctions between professional occupations in the public and private sectors, the use of professional knowledge and the image of profession in bureaucratic organizations, and the specific characteristics of professions that produce their own knowledge. In the discussion of the second point, professional occupations and their ideology are examined in relation to other occupations and to the possibilities of political awareness generated by uncertain professional statuses.